The role of morphine glucuronides in cancer pain.

Morphine metabolites are involved in various ways in determining the complex effects of morphine, both favourable and adverse, and may complicate the clinical use of morphine in the treatment of cancer pain. The production and effects of the principal morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, in both normal and pathological states have been reviewed in the current literature. Therapeutic implications are also reviewed on the basis of experimental and clinical reports. The presence of these metabolites should be recognized in the chronic treatment of cancer pain with morphine, especially in the presence of renal impairment, and should be considered to have an important influence on opioid responsiveness, defined as a balance between the achievement of an optimal analgesia and the occurrence of adverse effects.